Human respiratory syncytial virus (RSV) is a highly infectious member of the paramyxovirus family causing upper and lower respiratory tract infections. RSV infection is the leading cause of pulmonary disease of the lower respiratory tract (bronchiolitis, pneumonia and respiratory failure) in infants due to virus-induced airway damage and complex inflammatory processes and responsible for an estimated 160,000 deaths annually worldwide. RSV also causes morbidity and mortality to the immunocompromised and elderly populations. In the United States, an estimated 70,000 to 125,000 infants are hospitalized annually with RSV pneumonia or bronchiolitis resulting in costs that may well exceed US$400 million annually. Because of either low immunogenicity and/or for safety reasons, previous attempts to formulate a vaccine to prevent RSV-mediated disease have not been successful. The formalin-inactivated vaccine candidate (FI-RSV) induced severe disease upon subsequent natural infection with RSV. Vaccinated children were found to suffer from enhanced disease severity and even death upon subsequent RSV infection concomitant with pulmonary eosinophilia. Severe lung inflammatory responses characterized by a skewed CD4+ T-cell response (in the absence of neutralizing antibodies) and the influx of eosinophils in the lung were detected. Because of the unmet need of a safe and effective RSV vaccine, novel approaches are desperately needed. We have developed a patented mucosal vaccination platform that has demonstrated potent immune responses and protection against two different, mucosally challenged viruses. This powerful vaccine regimen can generate a Th1 biased, broad and potent humoral, mucosal and T cell responses including substantial mucosal secretory IgA and CTL. The uniqueness of our patented immunization regimen are:1) both mucosal (especially mucosal neutralizing antibodies), systemic immune responses and complete mucosal protection were raised without using any virus vectors and/or toxic adjuvants;2) no immunopathology or vaccine- enhanced diseases have been detected in virus challenged animals. Two patents on the platform technology have been granted. Mucosal HSV-2 vaccine patents are pending and being licensed to a vaccine developer for further product development. Therefore, this mucosal vaccine platform is an ideal candidate for developing a mucosal vaccine that protects against pathogens which enter at mucosal surfaces, as is the case for RSV. Using this patented mucosal immunization strategy, a safe and effective RSV vaccine will be developed. A strong scientific team involves four collaborating Institutes including: Biomedical Research Models, Inc., St. Jude Children's Research Hospital, University of Iowa and Sigmovir Biosystem, Inc. will: 1) prepare and optimize vaccine formulations to be tested in both BALB/c mice and cotton rats, 2) perform immunogenicity and protection studies in both mice and cotton rats of RSV intranasal infection, 3) test the durability of immune protection and the cross-subtype protection, 4) evaluate the safety (pulmonary histopathology) of the RSV vaccine candidate in both BALB/c mouse and the cotton rat models.
The Public Health Service (PHS) has recognized the significant public health issues caused by RSV. Due to the seriousness of RSV infection caused morbidity and mortality and the lack of a safe and effective RSV vaccine, development of novel approaches to RSV vaccination is desperately needed. The development of a safe and effective Respiratory Syncytial Virus (RSV) vaccine would provide protection to infants and elderly populations under the threat of RSV infection. The reduced incidence of disease in the lower respiratory tract would reduce the amount of medical costs directly associated with the infection.
| Yang, Kejian; Varga, Steven M (2014) Mucosal vaccines against respiratory syncytial virus. Curr Opin Virol 6:78-84 |
